Extracellular Matrix Biology 1

Question 1

What is ECM?

Answer 1

complex network of proteins and carbs between cells, includes fibrillar and non-fibrillar components

Question 2

ECM functions

Answer 2

physical support
determines mechanical and physiochemical properties of tissue
influences growth, adhesion and differentiation status
essential for development, tissue function and organogenesis

Question 3

What are the 3 components of connective issues?

Answer 3

collagens, multi adhesive glycoproteins, proteoglycans

Question 4

Name human disorders that result from a gene mutation affecting matrix proteins and the protein affected

Answer 4

osteogenesis imperfect - type 1 collagen
marfan's syndrome - fibrillar 1
alport's syndrome - type 4 collagen
epidermolysis bullosa - laminin 5
congenital muscular dystrophy - laminin 2

Question 5

Name a human disorder that result from a gene mutation affecting ECM catabolism and the protein affected

Answer 5

hurler’s Syndrome - L-alpha-iduronidase

Question 6

What happens to organ when there is excessive ECM deposition? give disease examples

Answer 6

fibrosis of the organ
liver fibrosis - cirrhosis
kidney fibrosis - diabetic nephropathy
lung fibrosis - silicosis

Question 7

Give an example of a disorder due to loss of ECM

Answer 7

osteoarthritis

Question 8

Name the connective tissues and their properties

Answer 8

tendon/skin - tough and flexible
vitreous humour - soft and transparent
bone - hard and dense
cartilage - resilient and shock absorbing

Question 9

What allows the different properties of connective tissues

Answer 9

ECM composition and components

Question 10

What are collagens?

Answer 10

family of fibrous proteins

Question 11

How can collagen resist tensile force?

Answer 11

successive layers at 90 degrees so resist force in all directions

Question 12

What is the structure of collagen?

Answer 12

3 alpha chains in left handed triple helix and may have one or more different alpha chains

Question 13

What is the alpha composition of type 1, 2 and 3 collagen?

Answer 13

type 1 - 2x alpha 1(I), 1x alpha 2(I)
type 2 - 3x alpha 1(II)
type 3 - 3x alpha 1(III)

Question 14

What is every third amino acid on the triple helix of collagen and why?

Answer 14

glycine as small enough to occupy interior

Question 15

What is required for lysine and proline hydroxylation? Why is it done?

Answer 15

Fe2+ and vitC for hydroxylases

contributes to interchain bond formation

Question 16

How are lysine and hydroxy-lysine modified? Why?

Answer 16

covalent cross linkages after secretion to increase strength

Question 17

What is the purpose of covalent cross links?

Answer 17

provide tensile strength and stability between or within the triple helix

Question 18

What do fibril associated collagens do? give examples

Answer 18

type IX or XII

associate with fibrillar collagens and regulate organisation of collagen fibrils

Question 19

what do network forming collagens do? give an example

Answer 19

type IV

assembles in a sheet like network in the basement membrane of all tissues with a varied molecular composition

Question 20

What is the structure of elastic fibres?

Answer 20

core (protein elastin) and microfibrils rich in fibrillin

interwoven with collagen to limit stretching

Question 21

What is the elastin structure?

Answer 21

hydrophobic segment and alpha helical segment
alpha helical rich in alanine and lysine
lysine side chains covalently linked

Question 22

What is the function of basement membrane?

Answer 22

regulate tissue function, surround muscle/nerve/fat cells

Question 23

Describe marfan’s syndrome

Answer 23

fibrillin-1 mutation reuslt in microfibril disruption

Question 24

Describe diabetic nephropathy

Answer 24

ECM accumulation so basement membrane thickens so renal filtration restricted and renal failure

Question 25

Describe alport syndrome

Answer 25

collagen type IV mutation so glomerulus basement membrane splits and laminated so decreased kidney function

Question 26

What is the basement membrane?

Answer 26

flexible, thin mats of ECM underlying epithelial sheets and tubes